TY - JOUR
T1 - Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
AU - Jones, Gregory T.
AU - Tromp, Gerard
AU - Kuivaniemi, Helena
AU - Gretarsdottir, Solveig
AU - Baas, Annette F.
AU - Giusti, Betti
AU - Strauss, Ewa
AU - van't Hof, Femke N. G.
AU - Webb, Thomas R.
AU - Erdman, Robert
AU - Ritchie, Marylyn D.
AU - Elmore, James R.
AU - Verma, Anurag
AU - Pendergrass, Sarah
AU - Kullo, Iftikhar J.
AU - Zy, Zi Ye
AU - Peissig, Peggy L.
AU - Gottesman, Omri
AU - Verma, Shefali S.
AU - Malinowski, Jennifer
AU - Rasmussen-Torvik, Laura J.
AU - Borthwick, Kenneth M.
AU - Smelser, Diane T.
AU - Crosslin, David R.
AU - de Andrade, Mariza
AU - Ryer, Evan J.
AU - McCarty, Catherine A.
AU - Bottinger, Erwin P.
AU - Pacheco, Jennifer A.
AU - Crawford, Dana C.
AU - Carrell, David S.
AU - Gerhard, Glenn S.
AU - Franklin, David P.
AU - Carey, David J.
AU - Phillips, Victoria L.
AU - Williams, Michael J. A.
AU - Wei, Wenhua
AU - Blair, Ross
AU - Hill, Andrew A.
AU - Vasudevan, Thodor M.
AU - Lewis, David R.
AU - Thomson, Ian A.
AU - Krysa, Jo
AU - Hill, Geraldine B.
AU - Roake, Justin
AU - Merriman, Tony R.
AU - Oszkinis, Grzegorz
AU - Galora, Silvia
AU - Saracini, Claudia
AU - Teijink, Joep A. W.
AU - Cardiogenics Consortium
AU - Int Consortium Blood Pressure
AU - Bown, Matthew J.
PY - 2017/1/20
Y1 - 2017/1/20
N2 - Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA.Objective: To identify additional AAA risk loci using data from all available genome-wide association studies.Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
AB - Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA.Objective: To identify additional AAA risk loci using data from all available genome-wide association studies.Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
KW - aortic aneurysm, abdominal
KW - computational biology
KW - genetics
KW - genome-wide association study
KW - matrix metalloproteinases
KW - meta-analysis
KW - CORONARY-ARTERY-DISEASE
KW - DENSITY-LIPOPROTEIN CHOLESTEROL
KW - ELECTRONIC MEDICAL-RECORDS
KW - CANDIDATE GENE ASSOCIATION
KW - RECEPTOR-RELATED PROTEIN-1
KW - HUMAN PREFRONTAL CORTEX
KW - C-REACTIVE PROTEIN
KW - SUSCEPTIBILITY LOCI
KW - SEQUENCE VARIANT
KW - TRANSCRIPTION FACTORS
U2 - 10.1161/CIRCRESAHA.116.308765
DO - 10.1161/CIRCRESAHA.116.308765
M3 - Article
C2 - 27899403
SN - 0009-7330
VL - 120
SP - 341
EP - 353
JO - Circulation Research
JF - Circulation Research
IS - 2
ER -